Profiling of extracellular vesicle-bound miRNA to identify candidate biomarkers of chronic alcohol drinking in nonhuman primates
Sloan A. Lewis
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA
Institute for Immunology, University of California Irvine, Irvine, California, USA
Search for more papers by this authorBrianna Doratt
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA
Institute for Immunology, University of California Irvine, Irvine, California, USA
Search for more papers by this authorSuhas Sureshchandra
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA
Institute for Immunology, University of California Irvine, Irvine, California, USA
Search for more papers by this authorTianyu Pan
Department of Statistics, University of California Irvine, Irvine, California, USA
Search for more papers by this authorSteven W. Gonzales
Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA
Search for more papers by this authorWeining Shen
Department of Statistics, University of California Irvine, Irvine, California, USA
Search for more papers by this authorKathleen A. Grant
Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA
Search for more papers by this authorCorresponding Author
Ilhem Messaoudi
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA
Institute for Immunology, University of California Irvine, Irvine, California, USA
University of Kentucky, 760 Press Avenue, Lexington, United States, 40536-0679 USA
Correspondence
Ilhem Messaoudi, Microbiology, Immunology and Molecular Genetics, College of Medicine, University of Kentucky, 760 Press Avenue, Lexington, KY 40536
Email: [email protected]
Search for more papers by this authorSloan A. Lewis
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA
Institute for Immunology, University of California Irvine, Irvine, California, USA
Search for more papers by this authorBrianna Doratt
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA
Institute for Immunology, University of California Irvine, Irvine, California, USA
Search for more papers by this authorSuhas Sureshchandra
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA
Institute for Immunology, University of California Irvine, Irvine, California, USA
Search for more papers by this authorTianyu Pan
Department of Statistics, University of California Irvine, Irvine, California, USA
Search for more papers by this authorSteven W. Gonzales
Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA
Search for more papers by this authorWeining Shen
Department of Statistics, University of California Irvine, Irvine, California, USA
Search for more papers by this authorKathleen A. Grant
Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA
Search for more papers by this authorCorresponding Author
Ilhem Messaoudi
Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, California, USA
Institute for Immunology, University of California Irvine, Irvine, California, USA
University of Kentucky, 760 Press Avenue, Lexington, United States, 40536-0679 USA
Correspondence
Ilhem Messaoudi, Microbiology, Immunology and Molecular Genetics, College of Medicine, University of Kentucky, 760 Press Avenue, Lexington, KY 40536
Email: [email protected]
Search for more papers by this authorFunding information
This study was supported by NIH 1R21AA025839-01A1 (Messaoudi), 5U01AA013510-20 (Grant), and 2R24AA019431-11 (Grant). S.A.L. is supported by NIH 1F31A028704-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Abstract
Background
Long-term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle-bound microRNAs (EV-miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease.
Methods
In this study, we profiled the plasma EV-miRNA content by miRNA-Seq from 80 nonhuman primates after 12 months of voluntary alcohol drinking.
Results
We identified a list of up- and downregulated EV-miRNA candidate biomarkers of heavy drinking and those positively correlated with ethanol dose. We overexpressed these candidate miRNAs in control primary peripheral immune cells to assess their potential functional mechanisms. We found that overexpression of miR-155, miR-154, miR-34c, miR-450a, and miR-204 led to increased production of the inflammatory cytokines TNFα or IL-6 in peripheral blood mononuclear cells after stimulation.
Conclusion
This exploratory study identified several EV-miRNAs that could serve as biomarkers of long-term alcohol drinking and provide a mechanism to explain alcohol-induced peripheral inflammation.
Graphical Abstract
Due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol use that could be used to determine drinking behavior prior to signs of overt organ damage. This study profiles the plasma EV-miRNA content of 80 non-human primates after 12 months of voluntary ethanol drinking by miRNA-Seq. We identified several EV-miRNA that could serve as biomarkers of long-term alcohol drinking as well as provided a mechanism for alcohol-induced peripheral inflammation.
CONFLICT OF INTEREST
No competing interests reported.
Supporting Information
| Filename | Description |
|---|---|
| acer14760-sup-0001-FigS1.pdfPDF document, 162.9 KB | Fig S1 |
| acer14760-sup-0002-FigS2.pdfPDF document, 416.7 KB | Fig S2 |
| acer14760-sup-0003-FigS3.pdfPDF document, 452.3 KB | Fig S3 |
| acer14760-sup-0004-TableS1.xlsxExcel 2007 spreadsheet , 75.9 KB | Table S1 |
| acer14760-sup-0005-TableS2.xlsxExcel 2007 spreadsheet , 11.4 KB | Table S2 |
| acer14760-sup-0006-TableS3.xlsxExcel 2007 spreadsheet , 18.6 KB | Table S3 |
| acer14760-sup-0007-SupLegends.docxWord 2007 document , 14 KB | Supplementary Material |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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